Intravenous immunoglobulins (IVIG) in severe/critical COVID-19 adult patients.

The coronavirus disease 2019 (COVID-19) pandemic has become a huge obstacle to the health system due to the high rate of contagion. It is postulated that intravenous immunoglobulins (IVIG) can lower the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammation and prevent the development of acute respiratory distress syndrome (ARDS). The main advantages of IVIG treatment might be targeting cytokine storm in severe and critical COVID-19 by influences on complement, innate immune cells, effector T-cells, and Tregs. Randomized clinical trials (RCTs) and non-RCTs evaluating the safety and efficacy of IVIG in patients with severe/critical COVID-19 were performed. It seems that early administration of high-dose IVIG (in the acceleration phase of the disease) in severe or especially critical COVID-19 may be an effective therapeutic option, but there are no strong data to use it routinely. The results regarding mortality reduction are inconclusive. Additionally, IVIG treatment carries a risk of complications that should be considered when initiating treatment. However, given the COVID-19 mortality rate and limited therapeutic options, the use of IVIG is worth considering. This review summarizes the development and highlights recent advances in treatment with IVIG of severe/critically ill COVID-19 patients.

Use of immunoglobulin replacement therapy in patients with secondary antibody deficiency in daily practice: a European expert Q&A-based review.

INTRODUCTION: Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established. To fill the gap and provide opinion and advice for daily practice, a group of experts met to discuss current issues and share best practical experience. AREAS COVERED: A total of 16 questions were considered that covered use of a tailored approach, definition of severe infections, measurement of IgG levels and specific antibodies, indications for IgRT, dosage, monitoring, discontinuation of IgRT, and Covid-19. EXPERT OPINION: Key points for better management SID should include characterization of the immunological deficiency, determination of the severity and degree of impairment of antibody production, distinguish between primary and secondary deficiency, and design a tailored treatment protocol that should include dose, route, and frequency of Ig replacement. There remains the need to carry out well-designed clinical studies to develop clear guidelines for the use of IgRT in patients with SAD.

Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial.

BACKGROUND: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern. In this context, as the present study will exploit pooled diversified convalescent plasma collected from recovered COVID-19 patients, the proposed hyperimmune Anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy would be able to counter new infectious COVID-19 variants by neutralizing the virus particles. After the successful outcome of the phase I/II clinical trial of C-IVIG, the current study aims to further evaluate the safety and efficacy of single low dose C-IVIG in severe COVID-19 patients for its phase II/III clinical trial. METHODS: This is a phase II/III, adaptive, multi-center, single-blinded, randomized controlled superiority trial of SARS-CoV-2 specific polyclonal IVIG (C-IVIG). Patients fulfilling the eligibility criteria will be block-randomized using a sealed envelope system to receive either 0.15 g/Kg C-IVIG with standard of care (SOC) or standard of care alone in 2:1 ratio. The patients will be followed-up for 28 days to assess the primary and secondary outcomes. DISCUSSION: This is a phase II/III clinical trial evaluating safety and efficacy of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) in severe COVID-19 patients. This study will provide clinical evidence to use C-IVIG as one of the first-line therapeutic options for severe COVID-19 patients. TRIAL REGISTRATION: Registered at clinicaltrial.gov with NCT number NCT04891172 on May 18, 2021.

Long-Term Outcomes after Vaccine-Induced Thrombotic Thrombocytopenia.

Vaccine-induced thrombotic thrombocytopenia (VITT), or thrombosis with thrombocytopenia syndrome (TTS), is a rare but serious complication of adenovirus-based vaccines against severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Observation of long-term outcomes is important to guide treatment of affected patients. This single-center consecutive cohort study included all patients diagnosed based on (1) vaccination 4 to 21 days before symptom onset, (2) signs or symptoms of venous or arterial thrombosis, (3) thrombocytopenia < 150/nL, (4) positive anti-platelet factor 4 (PF4) antibody, and (5) elevated D-Dimer > 4 times the upper limit of normal. Nine patients were enrolled. Acute management consisted of parenteral anticoagulants, corticosteroids, intravenous immunoglobulin (IVIG), and/or eculizumab. Eculizumab was successfully used in two patients with recurrent thromboembolic events after IVIG. Direct oral anticoagulants were given after hospital discharge. Median follow-up duration was 300 days (range 153 to 380). All patients survived the acute phase of the disease and were discharged from hospital. One patient died from long-term neurological sequelae of cerebral venous sinus thrombosis 335 days after diagnosis. Eight out of nine patients were alive at last follow-up, and seven had fully recovered. Anti-PF4 antibodies remained detectable for at least 12 weeks after diagnosis, and D-Dimer remained elevated in some patients despite oral anticoagulation. No recurrent thromboembolic events, other signs of VITT relapse, or bleeding complications occurred after discharge. In conclusion, VITT appears to be a highly prothrombotic condition. IVIG is not always successful, and eculizumab may be considered a rescue agent. Long-term management with direct oral anticoagulants appears to be safe and effective.

The effect of intravenous immunoglobulins on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Severe-to-critical COVID-19 has been associated with exaggerated immune responses, and anti-inflammatory agents including corticosteroid and interleukin-6 antagonist have been repurposed as the treatment modality against severe SARS-CoV-2 infections. However, the clinical efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of patients with COVID-19 was controversial. METHODS: This meta-analysis of randomized controlled trials (RCTs) investigated the effectiveness of IVIG in patients with COVID-19. Electronic databases were searched for RCTs that compared the clinical efficacy of IVIG with standard of care or placebo in the hospitalized patients with COVID-19 were included. RESULTS: Six RCTs involving 472 patients were included. Patients who received IVIG had a similar mortality rate to the controls (25.3% vs 27.0%, odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27-1.31). Compared with the control group, the study group demonstrated a similar incidence of receiving mechanical ventilation (OR, 0.70; 95% CI, 0.45-1.11), intensive care unit (ICU) admission (OR, 0.58; 95% CI, 0.22-1.53), length of hospital stay (mean difference [MD], -1.81 days; 95% CI, -8.42 to 4.81) and ICU stay (MD, -0.61 days; 95% CI, -2.80 to 1.58). CONCLUSIONS: The administration of IVIG in hospitalized patients with COVID-19 does not improve clinical outcomes.

Immune globulin therapy and kidney disease: Overview and screening, monitoring, and management recommendations.

PURPOSE: This report calls attention to the potential risks of diminished kidney function when administering immune globulin (IG). The goal is to increase awareness of chronic kidney disease (CKD) and kidney function impairment in patients receiving IG and provide recommendations for screening, monitoring, and management to promote risk prevention and mitigation. SUMMARY: Human IG preparations for intravenous (IVIG) or subcutaneous (SCIG) administration are the mainstay of treatment in patients with primary immunodeficiency diseases. Increasingly, IVIG at high doses (1,000 to 2,400 mg/kg) is also used as a treatment for a variety of autoimmune and inflammatory conditions. Although some autoinflammatory disorders respond to a single course of IVIG therapy, the majority of patients require long-term, regular infusions, thereby increasing the overall risks. Often, both patients and physicians treating adults with IG are unaware of underlying CKD or kidney function impairment. This lack of awareness constitutes a major risk factor for potential worsening, particularly when using high doses of IVIG. Therefore, screening of all patients for CKD and kidney function impairment before the use of IG is essential. Identification of the cause of kidney impairment is strongly encouraged, as IG therapy may need to be modified. CONCLUSION: As detailed here, there are potential risks to patients with impaired kidney function with administration of IG, particularly at high doses. Product selection, volume, route of administration, and rate of infusion may impact those with compromised kidney function. Therefore, screening of all patients for CKD and kidney function impairment before the use of IVIG and SCIG, as well as ongoing monitoring and management, is critical. As with all potential adverse drug reactions, the best approach is to prevent them.

A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe prothrombotic complication of adenoviral vaccines, including the ChAdOx1 nCoV-19 (Vaxzevria) vaccine. The putative mechanism involves formation of pathological anti-platelet factor 4 (PF4) antibodies that activate platelets via the low-affinity immunoglobulin G receptor FcγRIIa to drive thrombosis and thrombocytopenia. Functional assays are important for VITT diagnosis, as not all detectable anti-PF4 antibodies are pathogenic, and immunoassays have varying sensitivity. Combination of ligand binding of G protein-coupled receptors (protease-activated receptor-1) and immunoreceptor tyrosine-based activation motif-linked receptors (FcγRIIa) synergistically induce procoagulant platelet formation, which supports thrombin generation. Here, we describe a flow cytometry-based procoagulant platelet assay using cell death marker GSAO and P-selectin to diagnose VITT by exposing donor whole blood to patient plasma in the presence of a protease-activated receptor-1 agonist. Consecutive patients triaged for confirmatory functional VITT testing after screening using PF4/heparin ELISA were evaluated. In a development cohort of 47 patients with suspected VITT, plasma from ELISA-positive patients (n = 23), but not healthy donors (n = 32) or individuals exposed to the ChAdOx1 nCov-19 vaccine without VITT (n = 24), significantly increased the procoagulant platelet response. In a validation cohort of 99 VITT patients identified according to clinicopathologic adjudication, procoagulant flow cytometry identified 93% of VITT cases, including ELISA-negative and serotonin release assay-negative patients. The in vitro effect of intravenous immunoglobulin (IVIg) and fondaparinux trended with the clinical response seen in patients. Induction of FcγRIIa-dependent procoagulant response by patient plasma, suppressible by heparin and IVIg, is highly indicative of VITT, resulting in a sensitive and specific assay that has been adopted as part of a national diagnostic algorithm to identify vaccinated patients with platelet-activating antibodies.

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. CONCLUSIONS: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. WHAT IS KNOWN: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. WHAT IS NEW: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

A single center experience of intravenous immunoglobulin treatment in Covid-19.

BACKGROUND: Intravenous immunoglobulins (IVIg) have been used in management of severe Covid-19. Here in this study, we report our single-center experience regarding IVIg treatment in management of severe Covid-19. MATERIALS AND METHOD: Among hospitalized adult Covid-19 patients between April 1 and December 31, 2020, patients with confirmed diagnosis of Covid-19 who had Brescia-COVID respiratory severity scale score ≥ 3, hyperinflammation and received IVIg treatment in addition to standard of care were retrospectively investigated. We grouped IVIg recipients into three according to reasons for IVIg administration: Group 1 patients requiring anti-inflammatory treatment but complicated with secondary infection and/or sepsis , group 2 patients with Covid-19 related complications including progressive disease refractory to other anti-inflammatory agents, myocarditis, adult multisystem inflammatory syndrome, hemophagocytic lymphohystiocytosis like syndrome and group 3 patients with other complications non-specific to Covid-19. Mortality and clinical data was compared among groups. RESULTS: A total of 46 IVIg recipients were enrolled. Group 1 comprised 17 (36.9%), group 2 comprised 18 (39.1%) and group 3 comprised 11 (23.9%) patients. No significant differences in means of age, gender and comorbidities were observed among groups. Mortality was significantly lower in group 3 when compared to group 1 (64.7% vs 18.2%, p = 0.016) and close to significance when compared to group 2 (50% vs 18.2% p = 0.087). CONCLUSIONS: IVIg seemed to be used mostly in severe, refractory and complicated cases in our population. As a rescue agent in severe cases refractory to other anti-inflammatory strategies, 33.7% survival rate was observed with IVIg.

Mitigating the risk of COVID-19 exposure by transitioning from clinic-based to home-based immune globulin infusion.

PURPOSE: Intravenous immune globulin (IVIG) therapy is used in patients with hypogammaglobulinemia to lower the risk of infections. IVIG and subcutaneous IVIG (SCIG) therapy have been to shown to be safe and effective when administered as clinic-based infusions. Concern from both patients and providers for increased transmission of the coronavirus disease 2019 (COVID-19) virus to immunosuppressed patients with scheduled medical visits and procedures made it necessary for us to reassess our process of how we manage patient care in general and chronic clinic infusions in particular. Here we describe our experience of transitioning patients from clinic-based to home based IVIG and/or SCIG infusions to decrease the risk of COVID-19 exposure. METHODS: Criteria were developed to identify high-risk immunosuppressed patients who would be appropriate candidates for potential conversion to home based IVIG infusions. Data were collected via chart review, and cost analysis was performed using Medicare Part B reimbursement data. A patient outcome questionnaire was developed for administration through follow-up phone calls. RESULTS: From March to May 2020, 45 patients met criteria for home-based infusion, with 27 patients (60%) agreeing to home-based infusion. Posttransition patient outcomes assessment, conducted in 26 patients (96%), demonstrated good patient understanding of the home-based infusion process. No infusion-related complications were reported, and 24 patients (92%) had no concerns about receiving future IVIG and/or SCIG doses at home. No patient tested positive for COVID-19 during the study period. Clinic infusion visits decreased by 26.6 visits per month, resulting in a total of 106 hours of additional available infusion chair time per month and associated cost savings of $12,877. CONCLUSION: Transition of clinic based to home based IVIG/SCIG infusion can be successfully done to decrease potential exposure during a pandemic in a high-risk immunosuppressed population, with no impact on patient satisfaction, adherence, or efficacy. The home-based infusion initiative was associated with a reduction in costs to patients and an increase in available chair time in the infusion clinic.

Administration of intravenous immunoglobulin in the treatment of COVID-19: A review of available evidence.

Since December 31, 2019, unknown causes of pneumonia have been reported in Wuhan, China. This special pneumonia associated with a novel coronavirus was named 2019-nCoV by the World Health Organization (WHO) in January 2020. From the beginning of this infectious disease, clinicians and researchers have been endeavoring to discover an effective and suitable treatment for affected patients. To date, there is no definitive and specific treatments for coronavirus disease-19 (COVID-19) infection while drugs introduced are still in the clinical trial phase. Intravenous immune globulin (IVIG) is a biological product prepared from the serum and an optional treatment for patients with antibody deficiencies. In many countries, much attention has been paid to the use of IVIG in the treatment of patients with COVID-19. Due to the therapeutic importance of IVIG in virus infections, in the current study, we reviewed the possible effect of IVIG in viral infections and potential evidence of IVIG therapy in patients with COVID-19 virus.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. TRIAL DESIGN: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). PARTICIPANTS: The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 <300, and lung infiltrates >50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. INTERVENTION AND COMPARATOR: The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only MAIN OUTCOMES: The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. RANDOMISATION: Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. BLINDING (MASKING): Single blinded study, with participants blinded to allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. TRIAL STATUS: Current version of the protocol is "Version 2" dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

Pemphigus and COVID-19: Critical overview of management with a focus on treatment choice.

COVID-19 is a serious multisystem disease caused by severe acute respiratory syndrome coronavirus 2. Due to the COVID-19 crisis, that still keeps its impacts worldwide, numerous scheduled medical activities have been postponed and this interruption has a potential to modify the management of many cutaneous conditions including pemphigus. This narrative review aims to discuss the management of pemphigus in the era of COVID-19, considering the necessity to balance suitable pemphigus treatment with minimal risk of COVID-19-related mortality and morbidity. The data on the effect of treatments used for pemphigus on COVID-19 are limited. However, the evidence to manage patients properly is evolving and our knowledge is updated. Current expert recommendations include that patients with pemphigus should be informed clearly to avoid mismanagement and they should be monitored regularly for symptoms of COVID-19. Patients with mild disease can be managed with topical or intralesional corticosteroids, dapsone, or doxycycline. Systemic corticosteroids should be tapered to the lowest effective dose during the pandemic. Prednis(ol)one ≤10 mg/d can be continued in patients with COVID-19 while prednis(ol)one >10 mg/d may be reduced considering the activity of the disease. Conventional immunosuppressive therapies should only be discontinued in confirmed cases of COVID-19. Postponing rituximab treatment should be considered on a case by case basis. Intravenous immunoglobulin is not likely to increase the risk of infection and may be considered a safe option in patients with COVID-19. Given the psychological burden brought by COVID 19, online or face-to-face psychological support programs should be considered.